Sun Yan-Gang, Rupprecht Vanessa, Zhou Li, Dasgupta Rajan, Seibt Frederik, Beierlein Michael
Department of Neurobiology and Anatomy, McGovern Medical School, Houston, Texas 77030, Institute of Neuroscience, State Key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
Department of Neurobiology and Anatomy, McGovern Medical School, Houston, Texas 77030.
J Neurosci. 2016 Jul 27;36(30):7886-96. doi: 10.1523/JNEUROSCI.0409-16.2016.
Acetylcholine (ACh) signaling is involved in a wide range of processes, including arousal, attention, and learning. An increasing number of studies indicate that cholinergic control of these functions is highly deterministic, mediated by synaptic afferents that generate reliable and precise responses in postsynaptic neurons. However, mechanisms that govern plastic changes of cholinergic synaptic strength are poorly understood, even though they are likely critical in shaping the impact of cholinergic inputs on neuronal networks. We have recently shown that in the thalamic reticular nucleus (TRN), synaptic release of ACh generates excitatory-inhibitory biphasic postsynaptic responses, mediated by the activation of α4β2 nicotinic (nAChRs) and M2 muscarinic receptors (mAChRs), respectively. Here, using voltage-clamp recordings from TRN neurons in thalamocortical slices of mice, we demonstrate that the activation of Group I metabotropic glutamate receptors (mGluRs) by ambient or synaptically released glutamate evokes transient increases of nicotinic EPSCs. Additionally, we find that the selective Group I mGluR agonist DHPG [(S)-3,5-dihydroxyphenylglycine] evokes long-term potentiation of nicotinic EPSCs (mGluR-nLTP), dependent on increases in postsynaptic Ca(2+) concentration and the activation of phospholipase C. Both the induction and the maintenance of mGluR-nLTP require synergistic activation of mGluR1 and mGluR5. Together, our results show that postsynaptic Group I mGluRs are critically involved in the regulation of cholinergic synaptic strength on different time scales, suggesting that cholinergic control of local thalamic circuits is highly context-dependent and regulated by the overall levels of glutamatergic afferent activity.
Cholinergic signaling controls information processing and plasticity in neuronal circuits, but the mechanisms underlying the regulation of cholinergic synaptic strength on different time scales are unknown. Here we identify mGluR1 and mGluR5 as key elements in the dynamic regulation of cholinergic synaptic inputs onto neurons of the TRN. Our findings highlight potential mechanisms that regulate cholinergic signaling in the mammalian brain.
乙酰胆碱（ACh）信号传导参与多种过程，包括觉醒、注意力和学习。越来越多的研究表明，这些功能的胆碱能控制具有高度确定性，由在突触后神经元中产生可靠且精确反应的突触传入介导。然而，尽管胆碱能突触强度的可塑性变化机制可能对塑造胆碱能输入对神经网络的影响至关重要，但人们对此了解甚少。我们最近发现，在丘脑网状核（TRN）中，ACh的突触释放产生兴奋性 - 抑制性双相突触后反应，分别由α4β2烟碱型（nAChRs）和M2毒蕈碱型受体（mAChRs）的激活介导。在此，利用小鼠丘脑皮质切片中TRN神经元的电压钳记录，我们证明环境或突触释放的谷氨酸对I组代谢型谷氨酸受体（mGluRs）的激活会引起烟碱型兴奋性突触后电流（EPSCs）的瞬时增加。此外，我们发现选择性I组mGluR激动剂DHPG [（S） - 3,5 - 二羟基苯甘氨酸]会引起烟碱型EPSCs的长期增强（mGluR - nLTP），这依赖于突触后Ca（2 +）浓度的增加和磷脂酶C的激活。mGluR - nLTP的诱导和维持都需要mGluR1和mGluR5的协同激活。总之，我们的结果表明，突触后I组mGluRs在不同时间尺度上对胆碱能突触强度的调节中起关键作用，这表明局部丘脑回路的胆碱能控制高度依赖于背景且受谷氨酸能传入活动的总体水平调节。
胆碱能信号传导控制神经元回路中的信息处理和可塑性，但不同时间尺度上胆碱能突触强度调节的潜在机制尚不清楚。在这里，我们确定mGluR1和mGluR5是TRN神经元上胆碱能突触输入动态调节的关键要素。我们的发现突出了调节哺乳动物大脑中胆碱能信号传导的潜在机制。
